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PubMed1998

Treatment and prevention of venous thromboembolism.

Where available, low-molecular-weight heparin (LMWH) is the recommended approach for initial management of venous thromboembolism. When unfractionated heparin is administered, one of the cited heparin nomograms should be used to ensure that the heparin dose is sufficient to rapidly produce heparin levels in the therapeutic range for all patients. Because of the varying sensitivities of thromboplastins, each laboratory should correlate the activated partial thromboplastin time results with heparin's therapeutic range, which will correspond to 0.35 to 0.70 U of heparin/ml blood when using the antifactor Xa assay. Constant vigilance and a high level of suspicion are necessary to establish the clinical diagnosis of heparin-induced thrombocytopenia, and to institute appropriate therapy. When administering warfarin therapy, physicians should be aware of the sensitivity of the thromboplastin being used to provide the international normalized ratio (INR). To ensure that the patients are maintained within the target therapeutic range for INR (in most cases 2.0 to 3.0), the INR should be determined frequently, and the warfarin dosage should then be adjusted appropriately. Patients with an acute episode of venous thromboembolism should receive warfarin therapy for at least 3 months. At the present time, it is reasonable to treat the first recurrence with oral anticoagulants for 12 months and to indefinitely treat more than one recurrence. All patients at moderate to high risk for developing venous thromboembolism should receive prophylaxis. The approaches of proven value include low-dose heparin, LMWH, oral anticoagulants, and intermittent pneumatic compression.

Anticoagulants↗

PubMed1996

Effect of procainamide on pulmonary thromboembolism and platelet malondialdehyde in mice.

AIM: To study the effect of procainamide (PA) on pulmonary thromboembolism, platelet malondialdehyde (MDA) level and platelet aggregation induced by collagen and adrenaline. METHODS: Pulmonary thromboembolism, 2-thiobarbituric acid fluorescence micro-determination, conventional microscopic counting, and platelet aggregation test were used. RESULTS: PA (10-20 mg.kg-1) and mannitol (200 mg.kg-1) reduced thrombosis by 30%-75% and 75%, respectively. Thrombocytopenia followed thrombosis increased after the pretreatment of PA and mannitol. MDA decreased by both of them in vivo. In vitro, PA inhibited platelet aggregation and MDA production induced concentration-dependently by collagen and adrenaline. CONCLUSION: Inhibition of PA on pulmonary thromboembolism is involved in the decrease of platelet aggregation and MDA production.

Animals↗

PubMed2025

Venous thromboembolism laboratory testing (factor V Leiden and factor II c.∗97G>A), 2025 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. The etiology of VTE is multifactorial, including both environmental and genetic factors. Among the genetic factors, factor V Leiden and factor II c.∗97G>A (formerly referred to as prothrombin 20210G>A) are the 2 most common genetic variants associated with VTE. Testing for these variants is one of the most common referrals in clinical genetics laboratories. Although the methodologies for testing these 2 variants are relatively straightforward, the clinical implementation can be complicated regarding test indications, risk assessment for occurrence, and recurrence of VTE and related genetic counseling. This document provides an overview of VTE, information about the variants and their influence on risk, considerations before initiating genetic testing, and the clinical and analytical sensitivity and specificity of the tests. Key information that should be included in the laboratory report is also provided. This document supersedes the Technical Standards and Guidelines for Venous Thromboembolism Laboratory Testing originally published in 2005 and revised in 2018. It is designed for genetic testing professionals familiar with the disease and the analysis methods.

Humans↗

PubMed2004

Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTPH) is associated with considerable morbidity and mortality. Its incidence after pulmonary embolism and associated risk factors are not well documented. METHODS: We conducted a prospective, long-term, follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism. Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and, if supportive findings were present, ventilation-perfusion lung scanning and pulmonary angiography. CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg, respectively; pulmonary-capillary wedge pressure was normal; and there was angiographic evidence of disease. RESULTS: The cumulative incidence of symptomatic CTPH was 1.0 percent (95 percent confidence interval, 0.0 to 2.4) at six months, 3.1 percent (95 percent confidence interval, 0.7 to 5.5) at one year, and 3.8 percent (95 percent confidence interval, 1.1 to 6.5) at two years. No cases occurred after two years among the patients with more than two years of follow-up data. The following increased the risk of CTPH: a previous pulmonary embolism (odds ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic pulmonary embolism at presentation (odds ratio, 5.70). CONCLUSIONS: CTPH is a relatively common, serious complication of pulmonary embolism. Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed.

Adolescent↗

PubMed2004

Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines.

Although several authoritative, evidence-based, guidelines for the prevention of venous thromboembolism (VTE) have been published, the use of VTE prophylaxis in routine clinical practice varies markedly. Even in orthopedic surgery, the indication for which prophylaxis is used most often, a significant proportion of surgeons do not use routine prophylaxis. When prophylaxis is used, guideline recommendations are often not followed. A number of factors may contribute to the under-use of guidelines. Physician-related factors include: a lack of awareness of, or familiarity with, the guidelines; a perception that VTE is not a significant problem or that VTE prophylaxis is ineffective; and concern about potential bleeding risks. The guidelines may also be perceived to be too complicated or difficult to apply in a routine manner. In addition, a lack of facilities or resources may also present a barrier to implementation of the guidelines. A number of strategies are being investigated in an attempt to improve compliance with guidelines for VTE prophylaxis. For example, the Investigators Against Thromboembolism (INATE) initiative has developed a simplified pocket guideline on VTE prophylaxis in orthopedic and trauma surgery in order to raise awareness of the current guideline recommendations.

Cooperative Behavior↗

PubMed1999

Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism.

OBJECTIVES: To construct and validate the bleeding risk prediction score, which is based on variables identified in the literature that can be easily obtained before the institution of anticoagulant therapy, in a large independent cohort of patients who were treated with anticoagulant therapy for established venous thromboembolism to allow for quantitative assessment of the risks and benefits of the therapy and to adapt the patient's management accordingly. METHODS: We constructed a bleeding risk prediction score, based on variables and their odds ratios identified in the literature, which can be easily obtained before the institution of anticoagulant therapy (score = [ 1.6 X age] + [1.3 x sex] + [2.2 X malignancy]). Subsequently, we evaluated the score in a test group of 241 patients treated with anticoagulant therapy for venous thromboembolism to determine the optimal cutoff points for the prediction of hemorrhagic complications, using receiver operating characteristic curve analysis. We then validated this score in an independent cohort of 780 patients. A score of 3 or more points, 1 to 3 points, or 0 points represented a high, intermediate, or low bleeding risk, respectively. RESULTS: The score in about one fifth of the patients in the test group was classified as predicting high risk for bleeding complications. The risk of all bleeding complications was 26% in this group and the risk of major bleeding complications was 14%. The area under the curve was 0.75 (95% confidence interval, 0.64-0.84) and 0.82 (95% confidence interval, 0.66-0.98) for all bleeding complications and major bleeding complications, respectively. When validated, there was a moderate loss of predictive power of the score, but the categorization of the patients by the score remained clinically useful; 20% of the patients were classified as high risk, and the bleeding rate was 17% for all bleeding complications and 7% for major bleeding complications compared with 4% and 1%, respectively, in those categorized as low risk. CONCLUSIONS: With the use of 3 easily obtainable, clinical variables in a prediction model, it is possible to identify a subgroup of patients at the start of anticoagulant therapy who have a high risk of developing hemorrhagic complications. Further studies should address whether additional measures to prevent bleeding decrease the bleeding incidence without compromising efficacy.

Anticoagulants↗

PubMed2002

Preoperative or postoperative start of prophylaxis for venous thromboembolism with low-molecular-weight heparin in elective hip surgery?

BACKGROUND: Prophylaxis of venous thromboembolism with low-molecular-weight heparins in patients undergoing major orthopedic surgery is currently initiated according to at least 3 different regimens. In Europe, traditionally, prophylaxis is started 12 hours before surgery, whereas in North America it is initiated 12 to 48 hours postoperatively. The third regimen (perioperative) begins prophylaxis either earlier than 12 hours before or 12 hours after surgery. Unfortunately, the optimal regimen is uncertain because direct comparisons among these regimens with sufficiently large sample sizes are not available. OBJECTIVE: To assess, in a systematic review, the relative efficacy and safety of the 3 low-molecular-weight heparin regimens used to prevent thrombosis after total hip replacement. The incidence of postoperative thrombosis detected by contrast venography was used as the measure of efficacy and the rate of major bleeding was used as the measure of safety. METHODS: We pooled the results of all published studies, which met the following criteria: (1) inclusion of in at least 1 arm of the study of a dose of low-molecular-weight heparin that is approved for both preoperative and postoperative initiation of prophylaxis; (2) the use of mandatory bilateral contrast venography, performed between days 6 and 15 postoperatively; (3) thromboprophylaxis continued until venography; (4) independent reading of venograms; and (5) assessment of clinically overt major bleeding by predefined criteria. Articles were excluded if no separate data could be obtained for patients undergoing elective hip surgery (in case of patient mix), or if they were reported more than once. RESULTS: In the 1926 patients who used a preoperative regimen, the incidence of postoperative deep vein thrombosis was 19.2% (95% confidence interval [CI], 17%-21%). In the cohort of 925 patients who received a perioperative regimen, the rate of deep vein thrombosis was 12.4% (95% CI, 10%-14%), whereas in the group of 694 patients who received a postoperative regimen, it was 14.4% (95% CI, 12%-17%). The rate of major bleeding was 1.4% (95% CI, 1%-2%) in the preoperative group, 6.3% (95% CI, 5%-7%) in the perioperative group, and 2.5% (95% CI, 1%-3%) in the postoperative group. CONCLUSIONS: We find no convincing evidence that starting prophylaxis preoperatively is associated with a lower incidence of venous thromboembolism than starting postoperatively. Perioperative regimens may lower the risk of postoperative thrombosis, but if so, this positive effect is offset by an increase in postoperative major bleeding.

Anticoagulants↗

PubMed2006

Value of D-dimer testing for the exclusion of pulmonary embolism in patients with previous venous thromboembolism.

BACKGROUND: D-dimer levels remain elevated in many patients after completion of a 6-month anticoagulant drug course for a first episode of venous thromboembolism (VTE), which may limit the clinical usefulness of D-dimer testing for ruling out a possible recurrence. METHODS: We assessed the safety and usefulness of D-dimer testing in patients with suspected pulmonary embolism (PE) who had experienced a previous VTE. We analyzed data from 2 outcome studies that enrolled 1721 consecutive emergency department patients with clinically suspected PE. Information on the existence of a previous episode of VTE was abstracted from the database. All the patients underwent a sequential diagnostic workup, including an enzyme-linked immunosorbent assay D-dimer test and a 3-month follow-up. RESULTS: The proportion of confirmed PE was 24.1% (415/1719); PE was ruled out by a negative D-dimer test result in 32.7% (462/1411) of the patients without previous VTE but in only 15.9% (49/308) of the patients with previous VTE (P<.001). The 3-month thromboembolic risk was 0% (95% confidence interval, 0.0%-7.9%) in patients with previous VTE and a negative D-dimer test result. The 2-fold lower chance of a negative D-dimer test result in patients with previous VTE was independent of older age, active malignancy, fever, and recent surgery. CONCLUSIONS: In patients with suspected PE and previous VTE, a negative D-dimer test result seems to allow safely ruling out a recurrent event. However, the proportion of negative results is lower in such patients, definitely reducing the clinical usefulness of the D-dimer test in that subgroup.

Adult↗

PubMed2000

Safety of discontinuation of anticoagulation in patients with intracranial hemorrhage at high thromboembolic risk.

BACKGROUND: Limited data are available to guide the management of anticoagulation in patients with intracranial hemorrhage (ICH) at high thromboembolic risk. OBJECTIVE: To review the management of anticoagulation in patients with ICH at high thromboembolic risk. PATIENTS AND METHODS: We reviewed the management of anticoagulation in 141 patients who have a high risk of ischemic stroke and have ICH while taking warfarin. The 30-day risk of ischemic stroke while not taking anticoagulation treatment was determined using Kaplan-Meier survival estimates. RESULTS: The indications for anticoagulation were a prosthetic heart valve (52 patients [group 1]), atrial fibrillation and cardioembolic stroke (53 patients [group 2]), and a recurrent transient ischemic attack or an ischemic stroke (36 patients [group 3]). A prior ischemic stroke occurred in 14 (27%) of group 1 patients and in 23 (43%) of group 2 patients. Death occurred in 43% of the 141 patients. The median time not taking warfarin in this cohort was 10 days. Three patients had an ischemic stroke within 30 days of warfarin therapy discontinuation. Using Kaplan-Meier survival estimates, the probability of having an ischemic stroke at 30 days following warfarin therapy cessation in groups 1, 2, and 3 was 2.9% (95% confidence interval, 0%-8.0%), 2.6% (95% confidence interval, 0%-7.6%), and 4.8% (95% confidence interval, 0%-13.6%), respectively. In the 35 patients who had warfarin therapy restarted, none had recurrence of ICH during the same hospitalization. CONCLUSIONS: Discontinuation of warfarin therapy for 1 to 2 weeks has a comparatively low probability of embolic events in patients at high embolic risk. This should be taken into consideration when deciding whether to continue or discontinue anticoagulation in these patients at high embolic risk. Early recurrence of ICH is exceedingly uncommon.

Adult↗

PubMed1978

Thromboembolic risk of postsplenectomy thrombocytosis.

Although thrombocytosis is a very common finding after splenectomy, the thromboembolic risk of postsplenectomy thrombocytosis has not been clarified. To our knowledge, this retrospective study of 318 patients without myeloproliferative disorders who underwent splenectomy is the largest of its type. Thrombocytosis developed in 75% of the patients. No substantial increase in the incidence of thromboembolism was detected in patients with thrombocytosis.

Aspirin↗

PubMed1982

Venous thromboembolism prophylaxis: a survey of its use in the United States.

Despite controversy about their effectiveness, low-dose heparin therapy and elastic stockings were the methods most frequently selected by surgeons in a national survey on thromboembolism prophylaxis. These methods were selected even for patients with an extremely high risk of thrombosis. Surgeons responding to this survey apparently did not discriminate between degrees of patient risk, did not recognize the limitations of low-dose heparin and elastic stockings in protecting high-risk patients, and were unfamiliar with more effective methods of prophylaxis, ie, warfarin, dextran, and intermittent pneumatic compression. There is clearly a need for more specific data regarding the safe use of effective thromboembolism prophylaxis in surgical patients.

Anticoagulants↗

PubMed1983

Heparin with and without dihydroergotamine in prevention of thromboembolic complications of major abdominal surgery. A randomized trial.

We compared the results of dihydroergotamine mesylate administered with low-dose heparin sodium with those of low-dose heparin given alone in a randomized trial based on 181 patients who underwent major abdominal surgery. We found no significant difference in the incidence of thromboembolism between the two groups but a higher incidence of abnormal fibrinogen uptake test results in patients given heparin alone. There was no difference in hemoglobin levels and the number of blood transfusions. We concluded that there is little, if any, clinical advantage in adding dihydroergotamine to low-dose heparin to prevent thromboembolic complications in patients who have undergone major abdominal surgery.

Abdomen↗

PubMed1984

Role of intra-arterial streptokinase in treatment of arterial thromboembolism.

We treated 27 cases of arterial thromboembolism, including nine thrombosed grafts, with intra-arterial (IA) streptokinase. Complete lysis without significant residual lesions was achieved in eight (30%) of the cases, and partial lysis with sustained improvement was achieved in an additional six cases (22%). Partial lysis revealing inaccessible residual disease in runoff vessels occurred in four (15%) of the cases, and nine (33%) were primary failures. Surgery was completely avoided in 11 (41%) of the patients, lesser amputations were possible in three (11%), and 18 (67%) avoided major amputation. Grafts lysed faster (35 v 62 hours) and more frequently (seven [78%] of nine v 11 [61%] of 18) than native vessels, but had a higher rethrombosis rate (four [71%] of seven v two [11%] of 11) and a lower late patency rate (two [22%] of nine v nine [50%] of 18). Significant bleeding occurred in one (3.7%) of the patients, and major thromboembolic complications occurred in four (13.8%). None occurred in those treated with concomitant heparin sodium. Better patency and fewer complications were also observed in limbs that were not acutely threatened, when IA streptokinase infusion was completed within 48 hours, and when the occluded segment and runoff vessels were rendered widely patent by IA streptokinase, with the aid of balloon angioplasty when necessary (five [36%] of 14).

Arteries↗

PubMed1996

Low-dose heparin thromboembolism prophylaxis.

OBJECTIVE: To determine a rational approach to heparin dosing for thromboembolism prophylaxis. DESIGN: Literature review. RESULTS: Three commonly used heparin dosing regimens were identified: (1) standard low-dose heparin (5000 U administered subcutaneously 2-3 times per day); (2) adjusted-dose heparin (adequate to elevate the activated partial thromboplastin time to 5 seconds above the upper limit of normal); and (3) low-molecular-weight heparin (30 mg subcutaneously twice daily without monitoring). CONCLUSIONS: Adjusted-dose heparin thromboembolism prophylaxis is both the safest and most reliable method currently available.

Heparin↗

PubMed2006

Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation.

CONTEXT: Screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors is common clinical practice. Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A method covering multicausal thrombophilia is therefore required. OBJECTIVE: To investigate the relationship between recurrence of VTE and a simple global coagulation assay measuring thrombin generation. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 914 patients with first spontaneous VTE who were followed up for an average of 47 months after discontinuation of vitamin K antagonist therapy. The study was conducted at the Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, between July 1992 and July 2005. Thrombin generation was measured by a commercially available assay system. Patients with a previous or secondary VTE; antithrombin, protein C, or protein S deficiencies; presence of lupus anticoagulant; cancer; or pregnancy were excluded. MAIN OUTCOME MEASURE: Objectively documented symptomatic recurrent VTE. RESULTS: Venous thromboembolism recurred in 100 patients (11%). Patients without recurrent VTE had lower thrombin generation than patients with recurrence (mean [SD], 349.2 [108.0] nM vs 419.5 [110.5] nM, respectively; P<.001). Compared with patients who had thrombin generation greater than 400 nM, the relative risk (RR) of recurrence was 0.42 (95% confidence interval [CI], 0.26-0.67; P<.001) in patients with values between 400 nM and 300 nM; for patients with lower values, the RR was 0.37 (95% CI, 0.21-0.66; P = .001). After 4 years, the probability of recurrence was 6.5% (95% CI, 4.0%-8.9%) among patients with thrombin generation less than 400 nM compared with 20.0% (95% CI, 14.9%-25.1%) among patients with higher values (P<.001). Patients with thrombin generation less than 400 nM, representing two thirds of patients, had a 60% lower RR of recurrence than those with greater values (RR, 0.40; 95% CI, 0.27-0.60; P<.001). CONCLUSION: Measurement of thrombin generation identifies patients at low risk for recurrent VTE.

Adult↗

PubMed2006

Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the term given to any thromboembolic event (blocking of a blood vessel by a blood clot) occurring in the venous system. The current treatment recommended for VTE is anticoagulation (reduction of the blood's ability to clot). The aim of this review is to summarize results from randomized controlled trials (RCTs) for the effectiveness of anticoagulants (heparins, including low molecular weight heparins and vitamin K antagonists) in the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs) or placebo. OBJECTIVES: To examine the randomized controlled evidence for the effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli (PE) and the recurrence or extension of deep vein thrombosis (DVT). SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005). In addition, DKC also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: All randomized trials of anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or PE or both). DATA COLLECTION AND ANALYSIS: DKC and JM independently assessed trial quality and extracted data. JCP (biostatistician) analyzed the design elements and feasibility of a future randomized controlled trial to determine definitively efficacy and safety of anticoagulants in VTE treatment. MAIN RESULTS: Two RCTs were included. Data were not pooled because of heterogeneity between the studies. The two RCTs were too small to determine any difference in mortality, occurrence of pulmonary emboli, progression or return of DVT between patients treated with anticoagulation and those receiving no anticoagulation. AUTHORS' CONCLUSIONS: The limited evidence from RCTs of anticoagulants versus NSAIDs or placebo is inconclusive regarding the efficacy and safety of anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in clinical practice, so a further RCT comparing anticoagulants to placebo could not ethically be carried out.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Thromboembolic complications after splenectomy for hematologic diseases.

Thromboembolic complications following splenectomy for hematologic diseases occur in up to 10% of patients and may range from portal vein thrombosis (PVT) to pulmonary embolism (PE) and deep vein thrombosis (DVT). Up to now there exist no recommendations for the duration and intensity of prophylactic anticoagulation, which usually follows local institutional protocols. We report on three consecutive patients with severe portal vein thrombosis and/or pulmonary embolism--one with fatal outcome--7 to 35 days after splenectomy for autoimmune hemolytic anemia, immunothrombocytopenia, and indolent lymphoma, respectively. Incidence and pathophysiology of thromboembolic events (TE) in this patient group as well as prophylactic anticoagulation will be discussed, including a review of the current literature on this topic.

Adult↗

PubMed1989

Incidence of septic and thromboembolic-related deaths after splenectomy in adults.

In a review of 37,012 autopsies over the last 20 years 202 deceased adults who had had a splenectomy were investigated. The incidence of infections and thromboembolic complications related to death in these patients was compared with that of a matched deceased population (n = 403) who had not undergone splenectomy. Death-related pneumonia was diagnosed frequently in the splenectomy group and to a lesser extent in the control group (57.9 versus 24.1 per cent, P less than 0.001). Lethal sepsis with multiple organ failure occurred in 6.9 per cent of the splenectomy group and in 1.5 per cent of the controls (P less than 0.001). Purulent pyelonephritis was observed in 7.9 per cent of the splenectomy group and was significantly more frequent than in the control group with its rate of 2.2 per cent (P less than 0.001). Finally, pulmonary embolism was the major or a contributory cause of death more often in the splenectomy group than in the control group (35.6 versus 9.7 per cent, P less than 0.001). We conclude that splenectomy generates a considerable life-long risk of severe infection and of thromboembolism.

Adult↗